Analytical approach to heterogeneity correction factor calculation for brachytherapy

In brachytherapy treatment planning, the effects of tissue and applicator heterogeneities are commonly neglected due to lack of accurate, general, and fast three-dimensional (3D) dose-computational algorithms. A novel approach, based on analytical calculation of scattered photon fluxes inside and around a disk-shaped heterogeneity, has been developed for use in the three-dimensional scatter-subtraction algorithm. Specifically, our model predicts the central-ray dose distribution for a collimated photon isotropic source or brachytherapy "minibeam" in the presence of a slab of heterogeneous material. The model accounts for the lateral dimensions, location, composition, density, and thickness of the heterogeneity using precalculated scatter-to-primary ratios (SPRs) for the corresponding homogeneous problem. The model is applicable to the entire brachytherapy energy range (25 to 662 keV) and to a broad range of materials having atomic numbers of 13 to 82, densities of 2.7 g.cm-3 (Al) to 21.45 g.cm-3 (Pt) and thicknesses up to 1 mean free path. For this range of heterogeneous materials, the heterogeneity correction factors (HCFs) vary from 0.09 to 0.75. The model underestimates HCF when multiple scattering prevails and overestimates HCF when absorption dominates. However, the analytic model agrees with Monte Carlo photon transport (MCPT) benchmark calculations within 1.8% to 10% for 125I, 169Yb, 192Ir, and 137Cs for a wide variety of materials, with the exception of Ag. For 125I shielded by Ag, where the mean discrepancy can exceed 25%, the error is due to K-edge characteristic x rays originating within the heterogeneity. The proposed approach provides reductions in CPU time required of 5 x 10(4)-10(5) and 100 in comparison with direct MCPT simulation and 1D numerical integration, respectively. The limitations of model applicability, as determined by the physical properties of heterogeneity material and accuracy required, are also discussed.     

Enantiomeric separation of pirlindole by liquid chromatography using different types of chiral stationary phases

The enantioseparation of pirlindole by liquid chromatography (LC) was investigated using three different chiral stationary phases (CSPs) containing either cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-R), ovomucoid (OVM) or beta-cyclodextrin (beta-CD). The effects of the mobile phase pH on retention, enantioselectivity and resolution were studied. Methanol and acetonitrile were tested as organic modifiers while the influence of the addition to the mobile phase of sodium alkanesulfonates or sodium perchlorate was also investigated. Sodium perchlorate was only used on the Chiralcel OD-R column while sodium alkanesulfonates were tested as mobile phase additives on the three kinds of CSPs. The enantioseparation of pirlindole could be obtained on all CSPs tested, the best results with respect to chiral resolution being achieved on the Chiralcel OD-R and the OVM columns. The use of sodium octanesulfonate (NaOS) was found to improve the enantioseparation of pirlindole on the OVM column while enantioselectivity was considerably enhanced by addition of sodium perchlorate on the Chiralcel OD-R column.     

Undergraduate curriculum. SAEM Undergraduate Education Committee, Society for Academic Emergency Medicine

The specialty of emergency medicine (EM) is becoming more and more involved in medical school education. The previous article discusses the integration of EM in medical school curricula. This outline was developed by the SAEM Undergraduate Education Committee to offer specific goals and objectives as well as suggestions for implementation of EM concepts into medical school curricula.     

Electronic spin resonance detection of superoxide and hydroxyl radicals during the reductive metabolism of drugs by rat brain preparations and isolated cerebral microvessels

A spin trapping technique was used to analyze by electron spin resonance (ESR) the formation of oxygen-derived free radicals during the cerebral reductive metabolism of xenobiotics able to undergo a single electron reduction, i.e. quinones, pyridinium compounds and nitroheterocyclics. Paraquat, menadione and nitrofurazone were used as model compounds of these three classes of molecules. ESR spectra indicative of superoxide and hydroxyl radical formation were obtained by incubation of brain homogenates directly within the ESR cavity at 37 degrees C for each of the three molecules tested. These signals were dependent on nucleotide cofactors, and increased in a time-dependent manner. The NADPH and NADH dependent free radical production was further characterized in brain microsomal and mitochondrial fractions, respectively. By using various combinations of reactive species inactivating enzymes (superoxide dismutase, catalase), a metal chelator (deferoxamine), and an hydroxyl trapping agent (dimethylsulfoxide), it was shown that (1) the primary radical generated was the superoxide anion; and (2) a significant production of the hydroxyl radical also occurred, that was secondary to the superoxide anion production. Consistent signals indicative of the production of both oxygen-derived free radicals were obtained when isolated cerebral microvessels which constitute the blood-brain barrier were incubated with the model molecules. This is of particular toxicological relevance, because this barrier represents a key element in the protection of the brain, and is in close contact with blood-born exogenous molecules.     

Coronary stenting in unstable angina: early and late clinical outcomes

OBJECTIVE: To examine the procedural and long term success of coronary stenting in patients presenting with unstable angina and the effect of warfarin on the clinical outcome of these high risk patients. DESIGN: A nonrandomized, retrospective analysis of patients presenting with unstable angina. SETTING: A tertiary care, Canadian university-affiliated teaching hospital. PATIENTS: Of 1250 patients who underwent percutaneous transluminal coronary angioplasty between January 1994 and June 1995, 365 underwent coronary stenting. The study population consisted of the 156 patients presenting with unstable angina who underwent coronary stenting. Patients with Canadian Cardiovascular Society class IV and postinfarction angina were included. INTERVENTIONS: Stent delivery by standard techniques to the target lesion was successful in all patients. At discharge, 88 patients were prescribed warfarin, ticlopidine and acetylsalicylic acid (ASA); the remaining 68 patients received only ticlopidine and ASA. Late clinical outcomes were assessed by telephone interview. RESULTS: The overall procedural success rate was 96%. One patient died in hospital (0.6%). Other events were abrupt closure (1.9%), myocardial infarction (1.9%) and urgent bypass surgery (1.9%). During follow-up, target vessel reintervention was needed in 19.6% of patients. Early and late clinical outcomes did not differ significantly between anticoagulated patients and those treated with antiplatelet agents alone, but anticoagulated patients had a significantly longer hospital stay. CONCLUSIONS: Coronary stenting in patients with unstable angina was associated with excellent procedural success and favourable late clinical outcomes. Warfarin added no apparent additional clinical benefit to antiplatelet agents in this high risk population.     

The effect of autonomic nervous system activity on gastric myoelectrical activity: does the spectral reserve hypothesis hold for the stomach?

Cell proliferation is regulated by the cell cycle which is controlled by a number of cyclin-dependent kinases (CDKs). The functions of CDKs are critical for cell cycle and are required to traverse checkpoints. A network of inhibitors (CKI) of the cyclin-dependent kinases provide the important function of regulating the activity of the cyclin complexes. Deregulation of these results in either uncontrolled proliferation or cell death (apoptosis). Cell proliferation is an important factor in the development of carcinogenesis induced by genotoxic as well as nongenotoxic carcinogens. It is an integral part of the process of converting DNA adducts to mutations, it also decreases the time that is available for DNA repair and is required to clonal expansion of initiated cell populations. Moreover, cell proliferation increases the number of initiated cells by blocking cell death (apoptosis) and pertrubing checkpoints in the cell cycle. Two major mechanisms of induction of cell proliferation (regenerative and mitogens-stimulated) were discussed in relation to their potential roles in the carcinogenicity.     

Effects of surfactant distribution and ventilation strategies on efficacy of exogenous surfactant

The effects of both surfactant distribution patterns and ventilation strategies utilized after surfactant administration were assessed in lung-injured adult rabbits. Animals received 50 mg/kg surfactant via intratracheal instillation in volumes of either 4 or 2 ml/kg. A subset of animals from each treatment group was euthanized for evaluation of the exogenous surfactant distribution. The remaining animals were randomized into one of three ventilatory groups: group 1 [tidal volume (VT) of 10 ml/kg with 5 cmH2O positive end-expiratory pressure (PEEP)]; group 2 (VT of 5 ml/kg with 5 cmH2O PEEP); or group 3 (VT of 5 ml/kg with 9 cmH2O PEEP). Animals were ventilated and monitored for 3 h. Distribution of the surfactant was more uniform when it was delivered in the 4 ml/kg volume. When the distribution of surfactant was less uniform, arterial PO2 values were greater in groups 2 and 3 compared with group 1. Oxygenation differences among the different ventilation strategies were less marked in animals with the more uniform distribution pattern of surfactant (4 ml/kg). In both surfactant treatment groups, a high mortality was observed with the ventilation strategy used for group 3. We conclude that the distribution of exogenous surfactant affects the response to different ventilatory strategies in this model of acute lung injury.     

B cells directly tolerize CD8(+) T cells

This report investigates the response of CD8(+) T cells to antigens presented by B cells. When C57BL/6 mice were injected with syngeneic B cells coated with the Kb-restricted ovalbumin (OVA) determinant OVA257-264, OVA-specific cytotoxic T lymphocyte (CTL) tolerance was observed. To investigate the mechanism of tolerance induction, in vitro-activated CD8(+) T cells from the Kb-restricted, OVA-specific T cell receptor transgenic line OT-I (OT-I cells) were cultured for 15 h with antigen-bearing B cells, and their survival was determined. Antigen recognition led to the killing of the B cells and, surprisingly, to the death of a large proportion of the OT-I CTLs. T cell death involved Fas (CD95), since OT-I cells deficient in CD95 molecules showed preferential survival after recognition of antigen on B cells. To investigate the tolerance mechanism in vivo, naive OT-I T cells were adoptively transferred into normal mice, and these mice were coinjected with antigen-bearing B cells. In this case, OT-I cells proliferated transiently and were then lost from the secondary lymphoid compartment. These data provide the first demonstration that B cells can directly tolerize CD8(+) T cells, and suggest that this occurs via CD95-mediated, activation-induced deletion.     

Three-dimensional reconstruction of the human central sulcus reveals a morphological correlate of the hand area

OBJECTIVE: To examine the impact of ethnic group on aspects of weight concern and to assess the role of family values in explaining this association. SUBJECTS AND MEASURES: 20 Asian and 20 white daughters gave a questionnaire to their mother, father and sibling closest in age, concerning their profile characteristics (age, education) values and beliefs and completed a matched questionnaire containing additional measures of aspects of their weight concern. RESULTS: The results showed no differences between the white and Asian daughters in terms of either their restrained eating or body dissatisfaction. However, the results showed consistent differences between the members of the two family groups in terms of the value placed on achievement, child/parent relationships, competition, the role of women, and some differences in terms of materialism, the value of appearance and their idea of the perfect female body. The results were then analysed to assess the best predictors of the daughter's weight concern. Whereas restrained eating was related to the mother's rating of the value of physical appearance and the sibling's ratings of competitiveness and a non-traditional role for women (40% of the variance), the results showed that body dissatisfaction was related to the daughter's rating of materialism, having a father who preferred a thinner female body, the siblings ratings of a non-traditional role for women, degree of concordance within the family concerning the value of competitiveness and the educational level of the 'head of the family' (49% of variance). CONCLUSION: Whereas a dichotomous model of ethnicity may be insufficient to explain differences in aspects of weight concern, an expanded model of cultural beliefs may be a more powerful construct. Accordingly, the absence or presence of differences in weight concern according to ethnic group may simply reflect the extent to which the different groups chosen for analysis are differentiated by these predictive values.     

Modelling behavioral syndromes using Bayesian networks

In this paper Bayesian networks modelling is applied to a multidimensional model of depression. The characterization of the probabilistic model exploits expert knowledge to associate latent concentrations of neurotransmitters and symptoms. An evolution perspective is also considered. Specific criteria are introduced to detect the influence of the latent variable on the observation of symptoms. The Bayesian analysis is carried out using Gibbs sampling technique which is implemented in the BUGS software. The estimation phase leads to the selection of symptoms entering into the definition of behavioral syndromes. Results on real data are discussed. The last section deals with simulation experiments. Simulation results confirm our methodological choices. Results of the paper can enlarge to the central problem of the management of latent variables in Bayesian networks modelling.